Dynactin is a multi-subunit complex that has been implicated in the function of cytoplasmic dynein which is a minus end - directed microtubule motor protein with numerous functions including nuclear migration, mitotic spindle orientation, and cytoskeletal reorientation during interphase and mitosis. Dynamitin,the 50 kD subunit of dynactin, is important for stabilizing the dynactin complex. To gain more insight into the mechanism of stabilizing, we analyzed the sequence of dynamitin and revealed that domains of dynamitin is homology to the Walker A and Walker B ATPase motifs. The purified GST-dynamitin and GST-free dynamitin both showed ATPase activity specifically. An inactivating mutation in the Walker A, but not the Walker B ATPase motif abolished the ATPase activity of dynamitin. The mutational analysis studies further supported that dynamitin is an ATPase. Kinetic studies of the ATPase activity of dynamitin revealed a Km for ATP of 125.78μmol/L and a kcat of 7.4 min-1.

Aim To study the mechanism of inhibition of basic fibroblast growth factor (bFGF) related signal transduction by lidamycin in cancer cells. Methods MTT assay was used to determine the growth inhibitory effect of lidamycin (LDM) and adriamycin (ADR) in several cancer cell lines. The inhibition of bFGF bound to its receptor by LDM was measured with [ 125I ]-bFGF binding assay.Intracellular Ca2+ stimulated by bFGF was measured by Fura-3. The formation of bFGF- receptor immune complex and the inhibitory effect of LDM on the activity of PKC isoenzymes induced by bFGF in cancer cells were identified by Western blotting analysis. Results LDM displayed extremely potent growth inhibitory effect on several cancer cell lines in a dose-dependent manner. A comparison of the IC50 values showed that the effect of LDM was 1 000-fold more potent than that of ADR. LDM blocked the specific by anti-FGFR specific antibody, LDM inhibited the formation of bFGF-receptor immune complex. bFGF demonstrated that LDM inhibited the activity of PKC isoenzymes in cancer cells stimulated with bFGF.Conclusion The blocking of bFGF receptors in the signal transduction pathway may be involved in the effect of LDM on cancer cells.

Objective To investigate the duration for silicon gastric tube to indwell in stomach of aged patients.Methods One hundred elderly patients needing long-term nutrition support were equally randomized into two groups: control group and observation group.The former had the gastric tubes indwelled in the stomach for 4 weeks and the latter for 3 weeks.The two groups were compared about the used tubes in terms of the color of tube at the length of the first 10cm,the indentation by reflection for 10 seconds at the tube of first 10 cm,the hardness of the tube at the length of the first 10 cm and the springback angle of tube at the first 10cm after reflection.Results The tubes in the observation group were significantly better than those in the control group in terms of color,indentation,hardness and springback angle(all P<0?01).Conclusion The duration of indwelling silicon gastric tubes in stomach can be three weeks for old patients needing long-term nutrition support via indwelling silicon tubes in their stomach.

Objectives To explore the value of Silenz MRA in the follow-up assessment of intracranial aneurysms embolization. Methods Fifteen patients underwent coiled embolization were prospectively collected. Silenz and time of flight MRA (TOF MRA) were performed on the same day as DSA examination. Two neuro-radiologists scored the structures of peripheral vascular with a 4-score grading system and evaluate embolism status (two-grade montreal scale). The scores of vascular structures were compared using Wilcoxon signed rank tests. Weighted Kappa statistics was used to assess the inter-observer agreement on each MRA scoring, the inter-modality agreement between MRA and DSA, the inter-modality agreement between the MRA methods. Results There were 11 cases with complete occlusion, 4 cases with residual aneurysm revealed by DSA. For depiction, Silenz MRA was significantly better than TOF MRA [(3.50 ± 0.62) vs. (3.00 ± 0.63), Z=-3.12, P=0.002]. Inter-modality agreement of Silenz MRA and DSA was excellent (Kappa=0.82), while the agreement of TOF MRA and DSA was moderate(Kappa=0.60). Inter-modality agreement between Silenz MRA and TOF MRA was good (Kappa=0.76). Conclusions Silenz MRA is superior to TOF MRA for depiction of vascular structures and evaluation of embolism status, which is highly related with DSA. It has the value in the postoperative follow-up evaluation.

OBJECTIVETo investigate the changes of platelet mitochondria in rats with tourniquet-induced limb ischemia-reperfusion (IR) injury.

METHODSThirty SD rats were randomized equally into 5 groups including a control group and 4 limb IR injury groups for blood sampling at 2, 6, 12, or 24 h following IR injury induced by tourniquet on the thighs for 4 h. Platelet was separated from the blood samples for measurement of ATP content, mitochondrial membrane potentials, plasma cytochrome C level, and hydroperoxides.

RESULTSCompared with the control group, the rats with tourniquet-induced limb IR injury showed significantly decreased ATP content, lowered mitochondrial membrane potential, and increased plasma cytochrome C and hydroperoxide levels in the platelets at 2 and 6 h following the injury (P<0.05 or 0.01). These alterations recovered partially but remained significantly different from the control levels at 12 h (P<0.05 or 0.01) until full recovery at 24 h. Limb IR injury did not cause significant variations of the platelet counts.

CONCLUSIONTourniquet-induced limb IR injury can cause mitochondrial damage in the platelets, which occurs mainly in the early stage (6 h) and recovers gradually afterwards without significant impact on platelet counts.

Adenosine Triphosphate ; metabolism ; Animals ; Blood Platelets ; pathology ; Cytochromes c ; blood ; Hydrogen Peroxide ; metabolism ; Membrane Potential, Mitochondrial ; Mitochondria ; pathology ; Platelet Count ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; Tourniquets

Objective To investigate the relationship between serum levels of microRNA-130a(miR-130a),angiotensin Ⅱ(AngⅡ)and the degree of coronary artery lesions in patients with acute coronary syn-drome(ACS).Methods A total of 160 ACS patients admitted to the hospital from January 2021 to February 2023 were selected as the ACS group.According to total Gensini score,ACS patients were divided into mild group(57 cases),moderate group(54 cases)and severe group(49 cases).At the same time,160 healthy peo-ple were selected as the control group.The clinical data of all subjects were collected.The serum levels of miR-130a and AngⅡ were detected by real-time fluorescence quantitative PCR and enzyme-linked immunosor-bent assay,respectively.The clinical data and serum levels of miR-130a and AngⅡ were compared between control group and ACS group.The serum levels of miR-130a and AngⅡ were compared between ACS patients with different degrees of disease.Pearson correlation analysis was used to analyze the correlation between ser-um miR-130a level and AngⅡ in ACS patients.Multivariate Logistic regression was used to analyze the risk factors of ACS.Receiver operating characteristic curve was used to analyze the diagnostic value of serum miR-130a and AngⅡ levels for moderate and severe ACS.Results Compared with the control group,the ACS group had significantly higher proportions of patients with a history of hypertension and diabetes and signifi-cantly higher serum levels of miR-130a and AngⅡ(P<0.05).The serum levels of miR-130a and AngⅡ were increased sequentially in the mild group,moderate group and severe group(P<0.05).Serum miR-130a level was positively correlated with AngⅡ level in ACS patients(P<0.05).Hypertension,diabetes history and ele-vated serum levels of miR-130a and AngⅡ were independent risk factors for ACS(P<0.05).The area under the curve(AUC)of serum miR-130a,AngⅡ and their combination in the diagnosis of moderate ACS were 0.728,0.823 and 0.885,respectively,and the AUC of the combination of miR-130a and AngⅡ was higher than that of miR-130a,AngⅡ(P<0.05).The AUC of serum miR-130a,AngⅡ and their combination in the diagnosis of severe ACS were 0.731,0.730 and 0.825,respectively.The AUC of the combination of miR-130a and AngⅡ was higher than that of miR-130a and AngⅡ(P<0.05).Conclusion ACS patients serum miR-130-a,AngⅡ level is higher,and the serum miR-130a,AngⅡ levels are associated with the ACS degree of cor-onary artery lesions,the combination of the both degree of coronary artery lesions with high diagnostic value.

Objective:to apply Fuzhengkangai AIDS particles combined therapy with effective antiretroviral therapy (HAART) at the beginning of the HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome) patients,observe its clinical curative effect and improve the related adverse reactions.Methods:a multicenter,randomized,double-blind,placebo-controlled clinical research method,divided into experimental group and the control group (n =57),experimental group to "Fuzhengkangai particles" joint efficient antiretroviral therapy (HAART) antiviral treatment,control group to "Fuzhengkangai particles" placebo (5％ low dose) joint efficient antiretroviral therapy (HAART) antiviral treatment,treatment for 3 months.Two groups of patients with simultaneous liver and kidney function,blood routine,CD4 + T lymphocyte count,the observation of TCM symptoms and signs,survival quality of integral.Results:after 12 weeks of treatment,the control group and experimental group,the experimental group significantly elevated levels of peripheral blood RBC,lower levels of CR,reduce the signs and symptoms (total score,fatigue,stay,and spontaneous perspiration)integral,higher levels of CD4 + T lymphocyte count and survival quality score,the difference had statistical significance (p ＜ 0.05).Conclusion:Fuzhengkangai particles joint efficient antiretroviral therapy (HAART) antiviral treatment,can improve HAART after initial treatment of the patient's clinical symptoms,blood toxicity,the quality of survival,reduce the antiviral treatment of adverse reactions,combination drug alone can significantly increase the CD4 + T lymphocytes,so as to improve clinical curative effect.

Objective:To investigate the relationship between the blood test results of seven items of thyroid function and intolerance to 14 kinds of foods in physical examination population.Methods:Total of 45 764 participants who received physical examination and accepted 14-kind food intolerance and 7-item thyroid function detection from August 2016 to September 2019 in Chinese People′s Liberation Army General Hospital were included in this study. The data were analyzed based on age, gender, body mass index, smoking and drinking status, and laboratory test indexes. Chi square test and univariate or multivariate logistic regression were applied to analyze the correlation between food intolerance and thyroid function in the physical examination population.Results:In the subjects, there were 29 361 cases (64.16%) with at least intolerance to one kind of food, and 15 011 (32.80%) were in Grade 1, 9 037 (19.75%) in grade 2 and 5 313 (11.61%) in grade 3. The positive rate of egg intolerance was the highest (34.06%), and that of beef intolerance was the lowest (1.24%). Of the participants, 11 337 (24.77%) had at least one item thyroid dysfunction, among them, the highest abnormal rate was found in thyroid stimulating hormone (TSH), followed by anti-thyroglobulin antibodies and anti-thyroid peroxidase antibodies. The proportion (26.32%) of abnormal thyroid function in the participants with at least intolerance to one kind of food was significantly higher than that (22.00%) in the participants without intolerance to the 14 kinds of foods ( χ2=105.78, P<0.001). After adjusting for other significantly related factors, the positive results of intolerance to 14 kinds of foods was still the significant influencing factor of thyroid function abnormalities ( OR=1.14, Z=5.68, 95% CI: 1.09-1.20, P<0.001). Further analysis showed that, after adjusted for age, gender, smoking and drinking status, intolerance to four kinds of foods (egg, soybean, crab and pork) were the significant influencing factors of abnormal thyroid function. Conclusions:Food intolerance is an independent risk factor of thyroid dysfunction. Among them, egg, soybean, crab and pork may be the most important food varieties should be paid more attention to.

Objective:To evaluate the robustness of fully automated adaptive planning for Ethos online adaptive radiotherapy (ART) based on the intelligent optimization engine (IOE).Methods:Clinical data of 11 stage ⅠB cervical cancer patients admitted to Peking Union Medical College Hospital between June 2021 and June 2022 were retrospectively analyzed. Original planning images and iterative cone-beam computed tomography (iCBCT) images of each radiotherapy treatment were acquired, and all patient data were imported into the Ethos simulator. IOE-based 9-field automatic plan generation was performed for 11 patients using Ethos, and the generated plans were sent to online adaptive radiotherapy simulation to obtain each online adaptive radiotherapy plan (273 fractions in total) and complete the simulated treatment. For comparison, manual plan design was performed based on the images and contoured structures used for online adaptive radiotherapy planning, and the manually plans created with evenly divided 9 fields. Dosimetric parameters, plan complexity parameters, and Mobius quality assurance (QA) pass rates were collected to compare and evaluate the robustness of the online adaptive radiotherapy plan in terms of organs at risk (OAR), target volume dosimetric parameters, and plan complexity by using paired t-test or rank sum test. Results:The online adaptive plan of cervical cancer had comparable planning target volume (PTV) coverage compared to the manual plan. For the clinical target volume (CTV) D 99%, online adaptive plan was significantly higher than the manual plan [(45.93±0.36) vs. (45.32±0.31) Gy, P<0.001]. For hot dose area, the maximum point dose (PTV D max) of adaptive plan was significantly higher than the manual plan [(49.89±1.25) vs. (48.48±0.77) Gy, P<0.001], but the PTV D 1% of adaptive plan was significantly lower than the manual plan [(47.22±0.29) vs. (47.59±0.48) Gy, P<0.001]. There was no statistical difference in the conformal index ( P=0.967). And there was significant difference in the homogeneity index, with same medians and less dispersion in adaptive plan ( P<0.001). For OAR dose, bladder D mean, rectal V 40 Gy, small intestine D mean of adaptive plan was slightly higher than that of the manual plan; the rectal D mean, small intestine D 2 cm3 of the adaptive plan was slightly lower than that of manual plan; dosimetric parameters of right and left femoral heads, spinal cord and bone marrow of the adaptive plan were better than those of manual plan. The adaptive plan had more monitor units (MU) than the manual plan, but the complexity of the adaptive plan was significantly lower than that of the manual plan (0.135±0.012 vs. 0.151±0.015, P<0.001). For Mobius γ pass rate (5%/3 mm), both adaptive and manual plans met clinical requirements. Conclusion:Ethos cervical cancer online adaptive plan, which is based on the IOE engine, demonstrates good robustness and ensures the quality of online adaptive plans generated for each treatment fraction.

Objective:To evaluate the automatic optimization performance and clinical feasibility of the intelligent optimization engine (IOE) in the Ethos online adaptive radiotherapy platform.Methods:Clinical data of 11 patients with postoperative cervical cancer treated with Halcyon accelerator were retrospectively analyzed. Manual planning was performed for all patients using the 4 full arc volumetric modulated arc therapy (VMAT) (Manual-4Arc) in Eclipse, with a prescription dose of 45 Gy/25F. Patient images and structures were imported into the Ethos simulator, and appropriate clinical goals were added based on clinical requirements. The target coverage was normalized to 95%. Automatic plan generation was conducted using IOE, resulting in 7, 9, and 12 field intensity modulated radiotherapy (IMRT) plans (IMRT-7F、IMRT-9F、IMRT-12F), as well as 2 and 3 arc VMAT plans (VMAT-2Arc、VMAT-3Arc). Dosimetric index comparisons were made between the Manual-4Arc plans and the 5 groups of IOE-generated plans through one-way analysis of variance. Based on the analysis results, Turky post hoc multiple comparisons were performed to evaluate the automatic optimization performance of IOE.Results:In terms of the high dose area, the IMRT-12F plans showed the lowest D 1% for the planning target volume (PTV), and there were significant differences compared to the Manual-4Arc plans ( P=0.004). Regarding target coverage, all groups produced clinical target volume (CTV) plans that met the clinical requirements. Although the Ethos online adaptive plans were normalized during planning, the PTV coverage was slightly insufficient. For organs at risk (OAR) close to the target, such as the bladder, there were significant differences in V 30 Gy, V 40 Gy, and D mean among the 6 groups of plans. The dose ranking for the bladder was generally as follows: IMRT-12F